The myogenic response is crucial for maintaining vascular resistance to achieve constant perfusion during pressure fluctuations. Reduced cerebral blood flow has been reported in ischemic and nonischemic hemispheres after
stroke.
Ischemia-reperfusion injury and the resulting oxidative stress impair myogenic responses in the ischemic hemisphere. Yet, the mechanism by which
ischemia-reperfusion affects the nonischemic side is still undetermined. The goal of the present study was to determine the effect of
ischemia-reperfusion injury on the myogenic reactivity of cerebral vessels from both hemispheres and whether
protein nitration due to excess
peroxynitrite production is the underlying mechanism of loss of tone. Male Wistar rats were subjected to
sham operation or 30-min
middle cerebral artery occlusion/45-min reperfusion. Rats were administered saline, the
peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato
iron (III), or the nitration inhibitor
epicatechin at reperfusion. Middle cerebral arteries isolated from another set of control rats were exposed to ex vivo
oxygen-
glucose deprivation with and without
glycoprotein 91 tat (
NADPH oxidase inhibitor) or N(ω)-nitro-
l-arginine methyl ester. Myogenic tone and
nitrotyrosine levels were determined.
Ischemia-reperfusion injury impaired the myogenic tone of vessels in both hemispheres compared with the
sham group (P < 0.001). Vessels exposed to ex vivo
oxygen-
glucose deprivation experienced a similar loss of myogenic tone. Inhibition of
peroxynitrite parent radicals significantly improved the myogenic tone.
Peroxynitrite scavenging or inhibition of nitration improved the myogenic tone of vessels from ischemic (P < 0.001 and P < 0.05, respectively) and nonischemic (P < 0.01 and P < 0.05, respectively) hemispheres. Nitration was significantly increased in both hemispheres versus the
sham group and was normalized with
epicatechin treatment. In conclusion,
ischemia-reperfusion injury impairs vessel reactivity in both hemispheres via nitration. We suggest that
sham operation rather than the nonischemic side should be used as a control in preclinical
stroke studies.